Published ahead of print on August 28, 2008, doi:10.1165/rcmb.2007-0380OC
© 2009 American Thoracic Society DOI: 10.1165/rcmb.2007-0380OC Molecular Staging of Epithelial Maturation Using Secretory Cell–Specific Genes as Markers1 Center for Lung Regeneration, Department of Environmental and Occupational Health; 3 The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases, Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; and 2 Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina Correspondence and requests for reprints should be addressed to Barry R. Stripp, Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, 2075 MSRBII, 106 Research Drive, DUMC Box 103000, Durham, NC 27710. E-mail: Barry.Stripp{at}Duke.edu Bronchiolar Clara cells undergo phenotypic changes during development and in disease. These changes are poorly described due to a paucity of molecular markers. We used chemical and transgenic approaches to ablate Clara cells, allowing identification of their unique gene expression profile. Flavin monooxygenase 3 (Fmo3), paraoxonase 1 (Pon1), aldehyde oxidase 3 (Aox3), and claudin 10 (Cldn10) were identified as novel Clara cell markers. New and existing Clara cell marker genes were categorized into three classes based on their unique developmental expression pattern. Cldn10 was uniformly expressed in the epithelium at Embryonic Day (E)14.5 and became restricted to secretory cells at E18.5. This transition was defined by induction of CCSP. Maturation of secretory cells was associated with progressive increases in the expression of Fmo3, Pon1, Aox3, and Cyp2f2 between late embryonic and postnatal periods. Messenger RNA abundance of all categories of genes was dramatically decreased after naphthalene-induced airway injury, and displayed a sequence of temporal induction during repair that suggested sequential secretory cell maturation. We have defined a broader repertoire of Clara cell–specific genes that allows staging of epithelial maturation during development and repair.
Key Words: Clara • Claudin-10 • bronchiole • differentiation • lung development
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